Irradiation is a recognized method of inactivating infectious agents that could be used to rapidly create whole-organism vaccines that present multiple epitopes to generate effective immune responses. However, high dose irradiation required to ensure sterility can inflict oxidative damage on protein epitopes. The radiation-resistant bacterium, Deinococcus radiodurans, accumulates manganese-based complexes to protect against this radiation-induced oxidative damage. In 2012, we identified the ability of an optimized reconstituted Deinococcus-derived complex containing manganese, a decapeptide and phosphate (Mn-DP-Pi) to protect epitopes during exposure of viruses and bacteria to supralethal doses of gamma-radiation. We found that vaccination of mice with Staphylococcus aureus irradiated in the presence of Mn-DP-Pi resulted in protection against subsequent infection by inducing both cell-mediated and humoral immunity. These studies identify a novel and widely applicable method of creating immunogenic irradiated vaccines and open future avenues of investigation to further optimize such protective vaccines for translation into human use.